3-48599701-C-T

Variant names:

• chr3-48599701-C-T
• rs770254127
• NM_003365.3:c.1312G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003365.3(UQCRC1):​c.1312G>A​(p.Ala438Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A438S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UQCRC1 NM_003365.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47
• Publications: 0 publications found

Genes affected

UQCRC1 (HGNC:12585): (ubiquinol-cytochrome c reductase core protein 1) Enables ubiquitin protein ligase binding activity. Predicted to be involved in oxidative phosphorylation. Predicted to act upstream of or within mitochondrial electron transport, ubiquinol to cytochrome c. Located in mitochondrion. Implicated in Alzheimer's disease. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

UQCRC1 Gene-Disease associations (from GenCC):

• parkinsonism with polyneuropathy

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003365.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRC1	NM_003365.3	MANE Select	c.1312G>A	p.Ala438Thr	missense	Exon 12 of 13	NP_003356.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UQCRC1	ENST00000203407.6	TSL:1 MANE Select	c.1312G>A	p.Ala438Thr	missense	Exon 12 of 13	ENSP00000203407.5	P31930
	UQCRC1	ENST00000899333.1		c.1357G>A	p.Ala453Thr	missense	Exon 12 of 13	ENSP00000569392.1
	UQCRC1	ENST00000912156.1		c.1303G>A	p.Ala435Thr	missense	Exon 12 of 13	ENSP00000582215.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.13
Sift	Benign	0.075	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.33		Loss of helix (P = 0.2022)
MVP		0.35
MPC		0.32
ClinPred		0.92	D
GERP RS		4.8
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.36
gMVP		0.35
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs770254127; hg19: chr3-48637134;